Search

The effect of tachyphylaxis to angiotensin II amide on the pressor potency of angiotensin I, II and III and noradrenaline was investigated in conscious rabbits with indwelling cannulae. No significant difference was observed between the reduction in responses to angiotensin II (58 +/- 4%) and angiotensin III (42 +/- 6%) but angiotensin I (15 +/- 5 %) and noradernaline (17 +/- 10%) responses were less markedly inhibited. If all angiotensin I pressor activity was mediated through its conversion to angiotensin II one would expect an equivalent degree of cross-tachyphylaxis to occur with the two peptides. Our results suggest that angiotensin I may have significant inherent pressor activity of its own, independent of conversion. This compound is already known to have activity at other target tissues. The absence of a significant difference in the degree of tachyphylaxis with angiotensin II and III may indicate they have substantially common pathways as pressor agents.

Angiotensin I is known to have direct agonist activity at some target tissues, independent of its conversion to angiotensin II. Aspects of its possible direct role as a pressor agent were investigated in conscious rabbits. Phentolamine (3 mg/kg i.v.), a dose which did not affect baseline blood pressure, reduced the pressor response to angiotensin II by 17% (P less than 0.05) but did not alter the sensitivity to angiotensin I. Noradrenaline activity was reduced by 56%. Propranolol (2 mg/kg i.v.), a dose which did not affect baseline blood pressure but which substantially reduced the depressor response to isoprenaline, had no effect on the pressor activity of either angiotensin I or II. Noradrenaline potency was reduced by 32%. Hexamethonium (20 mg/kg i.v.), caused a potentiation of the response to angiotensin I and II and noradrenaline. This was probably a non-specific action associated with the decrease in baseline blood pressure. No differential effect of ganglion blockade on the two angiotensins was noted. The dissociation of the effects of phentolamine on angiotensins I and II provides further evidence that pressor actions of these two compounds act through partially different mechanisms.